RING-OPENED ADDUCTS OF THE ANTICANCER DRUG CARBOPLATIN WITH SULFUR AMINO-ACIDS

Reactions of the anticancer drug carboplatin (''Paraplatin'') with a v ariety of sulfur-containing amino acids have been investigated by H-1 and N-15 NMR spectroscopy and by HPLC. Thiols react very slowly and su lfur-bridged species containing four-membered Pt2S2 rings are the pred ominant products. In contrast, reactions with thioether ligands are mu ch more rapid, and kinetics for the initial stages of the reaction wit h L-methionine have been determined (k = 2.7 x 10(-3) M(-1) s(-1)). Su rprisingly, very stable ring-opened species are formed such as cis-[Pt (CBDCA-O)(NH3)(2)(L-HMet-S)] which has a half-life for Met-S,N ring-cl osure of 28 h at 310 K. A study of the formation of the analogous prod uct for N-acetyl-L-methionine and its subsequent ring closure is repor ted. Reactions such as these may play a role in the biological activit y of carboplatin.